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Hospital researchers identify gene important in certain cancers

Associate Professor Rob Richards and Research Assistant Sonia Dayan discussing results. Full size image available through contact

Researchers at the Women’s and Children’s Hospital, Adelaide have identified the FOR gene located on chromosome 16. This gene was found to have an important role in controlling when cells should divide.

Associate Professor Rob Richards who heads this research team at the hospital says, “Mutations in certain genes are critical in causing cancer. Specific areas on our chromosomes are unstable in cancer cells and genetic material is thought to be particularly unstable in regions known also as ‘fragile sites’.

“Of the 100 or so fragile sites in the human genome, we now know that one, the FRA16D fragile site, can be deleted in cancers of the stomach, colon, lung, breast and ovary.

Research Scientist Merran Finnis loads an agarose gel to identify DNA deletions. Full size image available through contact

“Our team has sequenced this fragile site and identified the FOR gene (short for Fragile Site OxidoReductase) as the main area of instability in the DNA (1,2). The FOR gene was found to code for multiple proteins. The gene is affected in various cancers including some cases of multiple myeloma,” Associate Professor Richards says.

Following on from the Women’s and Children’s Hospital’s identification of the FOR gene, a US research group(3)has found a function for one of the proteins produced by the FOR gene. The US studies have shown that one of these proteins enables cells to be more readily killed by tumour necrosis factor produced by the human body in response to infection and other conditions. If this FOR protein is not being produced, tumour cells are more likely to escape killing by the body’s defences.

Lynne Hobson, Research Scientist, splitting cells from a colon carcinoma cell line. Full size image available through contact

This same FOR protein was also found to be an essential partner to a second protein called p53 also involved in cancer. The p53 helps monitor DNA damage and puts a brake on cell division to enable the mutation to be repaired before the cell continues dividing. In this way mutations are not passed onto offspring cells. If either this FOR protein or p53 are absent due to deletion/mutation of their respective genes, then mutated cells can divide and proliferate unchecked, allowing development of a full-blown cancer.

Ongoing research by the hospital research team is aimed at discovering functions for the other FOR proteins. Once the roles of the proteins in both normal and cancer cells are established, Assoc Prof Richard’s team hopes that deletion in the FOR gene will be useful as a diagnostic tool for some cancers.

The research team’s ultimate hope is that their research will provide insights into human cancer which will result in new treatments.

The Women’s and Children’s Hospital has recently filed a patent on the FOR gene.

This research has been funded by grants from the National Health and Medical Research Council of Australia, the Women’s and Children’s Hospital Research Foundation and the Anti-Cancer Foundation of Australia.

References
1. Mangelsdorf et al(2000) Cancer Research 60: 1683-1689
2. Ried et al (2000) Human Molecular Genetics 9: 1651-1663
3. Chang et al (2000) Journal of Biological Chemistry published electronically October 31, 2000 as M007140200

To arrange interviews with Assoc Prof Richards contact:
Dr Edna Bates
Public Relations Officer Tel:(618) 8204 7388 email: batese@wch.sa.gov.au or
Ms Chris Ostermann
Director of Media and Community Relations
mobile 0401 125 630
ostermannc@wch.sa.gov.au
Women’s and Children’s Hospital- http://www.wch.sa.gov.au

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